Surufatinib in Combination With Iparomlimab and Tuvonralimab Injection and AG Chemotherapy for Neoadjuvant Therapy of HRPC or BRPC

NCT07833241 | Not Yet Recruiting Phase 2

• 1 other identifier: ZSPAC-22
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective, single-center, single-arm phase 2 study evaluating the efficacy and safety of neoadjuvant surufatinib plus iparomlimab and tuvonralimab injection and nab-paclitaxel/gemcitabine chemotherapy in patients with high-risk resectable or borderline resectable pancreatic cancer. Approximately 56 participants will be enrolled, including about 19 patients with high-risk resectable disease and 37 patients with borderline resectable disease. Participants will receive up to four 21-day cycles of neoadjuvant treatment. Participants considered eligible for surgery will undergo surgical resection approximately 4 weeks after neoadjuvant treatment. After surgery, adjuvant chemotherapy with either gemcitabine plus capecitabine or modified FOLFIRINOX will be selected by the investigators after multidisciplinary team review. The primary outcome is the 12-month event-free survival rate.

Conditions

Borderline Resectable Pancreatic Cancer; High-Risk Resectable Pancreatic Cancer

Keywords

Surufatinib; Iparomlimab and Tuvonralimab; Neoadjuvant; pancreatic cancer

Outcome Measures

Primary Outcomes (1)

• 12-month Event Free Survival (EFS) rate

  The starting point is the day of the first dose of neoadjuvant therapy, and observation continues until any of the following events occur (whichever comes first): 1. Disease progression (RECIST 1.1; re-evaluation is allowed if immune-related pseudoprogression is suspected); 2. Failure to complete the planned neoadjuvant therapy; 3. Inability to undergo surgery (including for non-disease reasons) or positive surgical margins; 4. Found to be unresectable during surgery; 5. Death for any reason.

  From the first dose through 12 months

Secondary Outcomes (9)

• Pathological complete remission rate (pCR)

  At postoperative pathological assessment, approximately 4 months after the first dose

• Major pathological remission rate (MPR)

  At postoperative pathological assessment, approximately 4 months after the first dose

• Objective Response Rate (ORR)

  Every 6 weeks (±7 days) from the first dose until disease progression or completion of neoadjuvant study treatment, assessed up to approximately 12 weeks.

• Disease Control Rate (DCR)

  Every 6 weeks (±7 days) from the first dose until disease progression or completion of neoadjuvant study treatment, assessed up to approximately 12 weeks.

• Event Free Survival (EFS)

  From the date of the first dose of neoadjuvant therapy to the first documented EFS event, assessed up to 36 months.

Study Arms (1)

Experimental Group

EXPERIMENTAL

All participants will receive up to four cycles of neoadjuvant surufatinib plus iparomlimab and tuvonralimab injection and AG chemotherapy. Eligible participants will undergo surgery approximately 4 weeks after neoadjuvant treatment. After surgery, participants will receive either GemCap or modified FOLFIRINOX adjuvant chemotherapy, as selected by the investigators.

Drug: Surufatinib Plus Iparomlimab and Tuvonralimab and AG Chemotherapy; Drug: Gemcitabine plus Capecitabine; Drug: Modified FOLFIRINOX

Interventions

Surufatinib Plus Iparomlimab and Tuvonralimab and AG Chemotherapy DRUG

Surufatinib 200 mg orally once daily; iparomlimab and tuvonralimab injection 5 mg/kg intravenously every 21 days; nab-paclitaxel 125 mg/m² and gemcitabine 1000 mg/m² intravenously on Days 1 and 8 of each 21-day cycle, for up to four cycles.

Experimental Group

Gemcitabine plus Capecitabine DRUG

After surgery, eligible participants may receive gemcitabine 1000 mg/m² intravenously on Days 1 and 8 plus capecitabine 1650-2000 mg/m²/day orally on Days 1-14 of each 21-day cycle.

Experimental Group

Modified FOLFIRINOX DRUG

After surgery, eligible participants may receive oxaliplatin 85 mg/m², irinotecan 150 mg/m², leucovorin 400 mg/m², and fluorouracil 2400 mg/m² every 14 days.

Experimental Group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have fully understood this study and voluntarily signed the informed consent form.
• Aged between 18 and 75 years inclusive, of any gender.
• Patients with high-risk resectable or borderline resectable pancreatic adenocarcinoma confirmed by histopathology or cytology. (The definition of borderline resectable pancreatic pancreatic cancer refers to the NCCN Guidelines 2026 (Version 1). High-risk resectable disease is defined as meeting all three of the following criteria:
• ① The tumor does not abut the portal vein-superior mesenteric vein (PV-SMV), or abuts the PV-SMV for \<180° with intact venous contour.
• ② The tumor does not abut arteries (celiac trunk, superior mesenteric artery, or common hepatic artery).
• ③ CA19-9 ≥ 500 U/mL or maximum diameter of primary tumor \> 3.0 cm.
• Have at least one measurable lesion per RECIST 1.1.
• No pathogenic BRCA1/2 or PALB2 mutations, or unknown BRCA1/2 and PALB2 mutation status.
• No prior systemic anti-tumor therapy or locoregional radiotherapy.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
• Expected survival ≥ 24 weeks.
• Absence of contraindications to surgery.
• Laboratory hematology parameters (without blood transfusion within the preceding 14 days):
• ① Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L; platelets ≥ 100 × 10⁹/L; hemoglobin ≥ 9 g/dL.
• ② Liver function: AST and ALT ≤ 2.5 × upper limit of normal (ULN); total bilirubin ≤ 1.5 × ULN. For patients with liver metastases, AST and ALT ≤ 5 × ULN.

You may not qualify if:

• Patients with distant metastasis.
• Patients who have received blood transfusion, blood products or hematopoietic growth factors (such as albumin and granulocyte colony-stimulating factor \[G-CSF\]) within 14 days prior to enrollment.
• Patients who have undergone any surgery or invasive treatment/procedure within 4 weeks prior to enrollment (except venous catheterization, puncture and drainage, etc.).
• Known hypersensitivity to any study drug.
• Uncontrolled hypertension defined as systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg.
• Patients with any disease or condition affecting drug absorption, or patients unable to receive oral surufatinib.
• Patients with active gastrointestinal diseases such as active gastric and duodenal ulcers, ulcerative colitis, or active bleeding from unresected tumors, or other conditions judged by the investigator to carry risks of gastrointestinal bleeding or perforation.
• Uncontrolled malignant ascites (defined as ascites that cannot be controlled by diuretics or paracentesis as assessed by the investigator).
• Patients with evidence or history of obvious bleeding tendency within 3 months prior to enrollment (bleeding \>30 mL within 3 months, hematemesis, melena, hematochezia), hemoptysis (fresh blood \>5 mL within 4 weeks), or thromboembolic events within 10 months (including stroke and/or transient ischemic attack \[TIA\]).
• Clinically significant electrolyte abnormalities as judged by the investigator.
• Significant clinically relevant cardiovascular diseases, including but not limited to: acute myocardial infarction, severe/unstable angina or coronary artery bypass grafting within 6 months prior to enrollment; New York Heart Association (NYHA) class \>2 congestive heart failure; ventricular arrhythmias requiring pharmacological treatment; left ventricular ejection fraction (LVEF) \<50%.
• History of other malignancies within the past 5 years, except for radically resected basal cell carcinoma or squamous cell carcinoma of the skin, or carcinoma in situ of the cervix.
• Active or uncontrolled severe infections:
• ①Known human immunodeficiency virus (HIV) infection;
• ②Known history of clinically significant liver disease, including viral hepatitis. ③Known hepatitis B virus (HBV) carriers must be excluded if there is active HBV infection, i.e., positive HBV DNA (\>1×10⁴ copies/mL or \>2000 IU/mL); Known hepatitis C virus (HCV) infection with positive HCV RNA (\>1×10³ copies/mL), or other hepatitis, liver cirrhosis.

Sponsors & Collaborators

• Shanghai Zhongshan Hospital: lead

Study Sites (1)

Shanghai Zhongshan Hospital

Shanghai, 200000, China

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

surufatinib; Gemcitabine; Capecitabine

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Central Study Contacts

Liang Liu, M.D. Ph.D

CONTACT

021-64041990; liu.liang@zs-hospital.sh.cn

Xu Han, M.D. Ph.D

CONTACT

021-64041990; han.xu1@zs-hospital.sh.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 10, 2026
• First Posted: September 22, 2026
• Study Start: September 1, 2026
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): September 1, 2029
• Last Updated: September 22, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)